Berberine partially ameliorates cardiolipotoxicity in diabetic cardiomyopathy by modulating SIRT3‐mediated lipophagy to remodel lipid droplets homeostasis

作者：Wenxian Chen, Tongzhu Jin, Yilin Xie, Changsheng Zhong, Huiying Gao, Lei Zhang, Jin Hyun Ju, Ting Cheng, Mengyang Li, Huifang Wang, Zhenbo Yang, Qin Deng, Zhimin Du, Haihai Liang · 发表于：British Journal of Pharmacology · 年份：2025 · DOI：10.1111/bph.70035 · 被引用次数：22 · 研究领域：Lipid metabolism and biosynthesis、Autophagy in Disease and Therapy、Sirtuins and Resveratrol in Medicine

BACKGROUND AND PURPOSE: Emerging evidence indicated that the excessive lipid droplets (LDs) accumulation and lipotoxicity play a significant role in the development of diabetic cardiomyopathy (DCM), yet the regulatory mechanisms governing the function of cardiac LDs are still unknown. Lipophagy has been shown to be involved in the maintenance of LDs homeostasis. The objective of this study was to explore the mechanism of lipophagy in cardiomyocytes and investigate whether berberine could mitigate DCM by modulating this pathway. EXPERIMENTAL APPROACH: Bioinformatics analysis identified disorders of lipid metabolism and autophagy in DCM. To carry out further research, db/db mice were utilized. Furthermore, H9C2 cells treated with palmitic acid were employed as a model to explore the molecular mechanisms involved in myocardial lipotoxicity. KEY RESULTS: The results showed that lipophagy was impaired in DCM. Mechanistically, sirtuin 3 (SIRT3) was demonstrated to regulate lipophagy in cardiomyocytes. SIRT3 was down-regulated in DCM. Conversely, activation of SIRT3 by the activator nicotinamide riboside (NR) could promote lipophagy to alleviate PA-induced lipotoxicity in H9C2 cells. Moreover, berberine administration markedly mitigated diabetes-induced cardiac dysfunction and hypertrophy in db/db mice, which dependent on SIRT3-mediated lipophagy. CONCLUSION AND IMPLICATIONS: Collectively, SIRT3 could moderate cardiac lipotoxicity in DCM by promoting lipophagy, suggesting that the r...